GABARAPs

GABARAPs, short for gamma-aminobutyric acid receptor-associated protein-like proteins, are a subfamily of the Atg8 family of ubiquitin-like proteins that regulate autophagy in eukaryotic cells. In mammals, the best-characterized members are GABARAP, GABARAPL1, and GABARAPL2 (also known as GATE-16); a fourth paralog, GABARAPL3, has been described in some species but remains less well studied. GABARAPs share a common fold and are co-opted into the autophagy machinery alongside LC3 proteins.

Like other Atg8 proteins, GABARAPs are synthesized as precursors and processed by Atg4 to expose a C-terminal glycine, enabling conjugation to phosphatidylethanolamine on expanding autophagosomal membranes. The lipidation reaction proceeds through the Atg7–Atg3 ubiquitin-like cascade and is reversible by Atg4. Lipidated GABARAPs decorate autophagosomes and are involved in their maturation and trafficking toward lysosomes.

In terms of function, GABARAPs are thought to act at later stages of autophagy compared with LC3 proteins, promoting membrane tethering and SNARE-mediated fusion with lysosomes. They participate in selective autophagy by interacting with cargo receptors bearing LC3-interacting region motifs and may help recruit other factors required for efficient autophagosome-lysosome fusion. GABARAPs also contribute to processes such as mitophagy and xenophagy under specific cellular conditions.

Regulation of GABARAP expression and activity integrates with broader cellular stress and nutrient-sensing pathways. Alterations in GABARAP function have been linked to various disease contexts, including neurodegenerative disorders and cancer, making them a focus of autophagy research.